The primary placental defect in preeclampsia is shallow trophoblast invasion of the decidua leading to incomplete vascular transformation and inadequate uteroplacental perfusion. Soluble fms-like tyrosine kinase- 1 (sFlt-1) seems to interfere with these events by inhibiting local angiogenesis and/or by impeding trophoblast invasion. Preeclampsia is also associated with maternal thrombophilias and decidual hemorrhage, which form thrombin from decidual cell-expressed tissue factor. Although sFlt-1 is highly expressed by trophoblasts, sFlt-1 expression has not been studied in decidual cells, which are the predominant cell type encountered by invading trophoblasts. Here, we demonstrate that isolated decidual cells express sFlt-1 mRNA, suggesting that they can synthesize sFlt-1. Moreover, in first trimester decidual cells, thrombin enhanced sFlt-1 mRNA levels, as measured by quantitative reverse transcriptase-polymerase chain reaction, and levels of secreted sFlt-1 protein, as measured by enzyme-linked immunosorbent assay. The thrombin antagonist hirudin blocked this effect, demonstrating that active thrombin is required. Emphasizing the specificity of the thrombin response, neither interleukin-1 nor tumor necrosis factor- affected sFlt-1 expression in the decidual cells. In contrast to first trimester decidual cells, thrombin did not affect sFlt-1 levels in cultured term decidual cells. In early pregnancy, thrombin may act as an autocrine/paracrine enhancer of sFlt-1 expression by decidual cells to promote preeclampsia by interfering with local vascular transformation.

Lockwood, C.j., Toti, P., Arcuri, F., Norwitz, E., Funai, E.f., Huang, S.t., et al. (2007). Thrombin regulates soluble fms-like tyrosine kinase-1 (sFlt-1) expression in first trimester decidua: implications for preeclampsia. THE AMERICAN JOURNAL OF PATHOLOGY, 170, 1398-1405 [10.2353/ajpath.2007.060465].

Thrombin regulates soluble fms-like tyrosine kinase-1 (sFlt-1) expression in first trimester decidua: implications for preeclampsia.

TOTI, PAOLO;
2007

Abstract

The primary placental defect in preeclampsia is shallow trophoblast invasion of the decidua leading to incomplete vascular transformation and inadequate uteroplacental perfusion. Soluble fms-like tyrosine kinase- 1 (sFlt-1) seems to interfere with these events by inhibiting local angiogenesis and/or by impeding trophoblast invasion. Preeclampsia is also associated with maternal thrombophilias and decidual hemorrhage, which form thrombin from decidual cell-expressed tissue factor. Although sFlt-1 is highly expressed by trophoblasts, sFlt-1 expression has not been studied in decidual cells, which are the predominant cell type encountered by invading trophoblasts. Here, we demonstrate that isolated decidual cells express sFlt-1 mRNA, suggesting that they can synthesize sFlt-1. Moreover, in first trimester decidual cells, thrombin enhanced sFlt-1 mRNA levels, as measured by quantitative reverse transcriptase-polymerase chain reaction, and levels of secreted sFlt-1 protein, as measured by enzyme-linked immunosorbent assay. The thrombin antagonist hirudin blocked this effect, demonstrating that active thrombin is required. Emphasizing the specificity of the thrombin response, neither interleukin-1 nor tumor necrosis factor- affected sFlt-1 expression in the decidual cells. In contrast to first trimester decidual cells, thrombin did not affect sFlt-1 levels in cultured term decidual cells. In early pregnancy, thrombin may act as an autocrine/paracrine enhancer of sFlt-1 expression by decidual cells to promote preeclampsia by interfering with local vascular transformation.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11365/25039
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